Inhibition of the hepatocyte uptake of radiolabelled monoclonal antibodies by chelating agents.
The imaging of small abdominal tumours with indium 111 labelled monoclonal antibodies (MAbs) is often obscured by the uptake of activity into the heptocytes of normal liver tissue. A model has therefore been developed to analyse reagents which may inhibit the hepatocyte uptake of 111In-MAb whilst preserving tumour uptake. Primary rat hepatocyte cultures and an epithelial membrane antigen (EMA) expressing tumour cell line (MCF7), recognised by the EMA-specific MAb ICR2, were obtained in tissue culture. Monolayers of both cells were incubated with the 111In-MAb with or without the additional reagents and the cell uptake then measured and expressed per milligram of cell protein using a Lowry protein assay. No preferential reduction in hepatocyte uptake was noted by incubating cells with either saturated or unsaturated transferrin. The chelating agent, diethylene triamine penta-acetic acid (DTPA), however, significantly reduced the uptake of activity in hepatocytes but not the tumour cell line (P less than 0.05). An optimum concentration and time period for incubating DTPA with labelled MAb was established. The mean hepatocyte uptake was reduced by 80% with a 1 h incubation with 1 mM DTPA. These results suggest that DTPA may have a role in reducing the liver uptake of radioactivity in patient studies using 111In-MAb.
Davidson
B R
BR
Department of Surgery, University College and Middlesex School of Medicine, London, UK.
Boulos
P B
PB
Porter
J B
JB
D000818:Animals; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology*; D007205:Indium Radioisotopes; D008099:Liver / Q000000981:diagnostic imaging*; D008297:Male; D004369:Pentetic Acid / Q000494:pharmacology*; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D007205:Indium Radioisotopes; D004369:Pentetic Acid